Estimation of growth fraction in situ in human bladder cancer with bromodeoxyuridine labelling

A group of 8 patients with invasive bladder cancer received fractionated intra-arterial infusions of the thymidine analogue bromodeoxyuridine (BrdU), 150 mg, every 6 to 10 h for 3 days before endoscopic cold cup biopsy to label tumour cells in the proliferative pool (growth fraction). The tumour specimens were fixed and stained by an indirect immunoperoxidase method using anti-BrdU monoclonal antibody. There was an area which could not be stained with anti-BrdU monoclonal antibody surrounding the stained area where diffusion effects could be excluded. This indicates a growth fraction less than 1 and implies that a proportion of the tumour cells in bladder tumours are cycling and contributing to growth. The BrdU labelling index (growth fraction) was determined by counting the number of BrdU labelled cells in the well labelled tissue sections. The average growth fraction of invasive bladder cancer was 38.4 +/- 7.7% (range 26.9-48.1%). Grade 3 tumours averaged 42.8 +/- 5.4% labelling versus 31.0 +/- 4.4% in grade 2. The higher growth fraction may indicate greater biological malignancy. These results indicate that immunohistochemical studies of cell kinetics using BrdU monoclonal antibodies may provide information about the biological characteristics of bladder tumours in situ.